Abstract
Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders which affects the hippocampus and cortical neurons leading to impairment of cognitive ability. Treatment of AD depends mainly on acetylcholinesterase inhibitors, however, a novel therapeutic approach is introduced based on the maintenance of neuronal viability and functionality exerted through neurotrophic factors. In the current study, Ulmus pumila L. leaves alcoholic extract was investigated for its neuroprotective activity in AlCl3-induced AD in rats. Rats were orally treated with AlCl3 (17 mg/kg) for 4 weeks followed by U. pumila extract (150 mg/kg b.wt.) for another 6 weeks. Treatment of neuro-intoxicated rats with U. pumila extract resulted in a significant regulation in neurotrophic factors; brain derived neurotrophic factor and transforming growth factor-β and pro-inflammatory cytokine; TNF. It also induced an elevation in serum levels of monoamine neurotransmitters; norepinephrine, dopamine and serotonin and a decline in brain acetlycholinesterase activity. U. pumila extract also showed potent antioxidant activity as indicated by the declined malondialdehyde and elevated reduced glutathione, catalase and super oxide dismutase levels in AD rats‘ brains. Histological improvement was detected in the cerebral cortex, the hippocampus and striatum of the treated rats. The phytochemical analysis of U. pumila extract revealed high contents of flavonoids and phenolics and the major compounds were isolated and chemically characterized. Additionally, U. pumila extract and the isolated compounds exerted a prominent activity in in-vitro acetylcholinesterase inhibition assay with kaempferol-3-O-β-glucoside being the most potent compound showing IC50 of 29.03 ± 0.0155 μM. A molecular docking study indicated high affinity of kaempferol-3-O-β-robinobioside on acetylcholine esterase binding site with estimated binding free energy of –8.26 kcal/mol.
Highlights
Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders (Calsolaro et al, 2019)
Ulmus pumila L. leaves showed cytotoxicity against human breast cancer cell line indicating its chemotherapeutic potential through induction of apoptosis (Hussien et al, 2019) This study aims to inspect the therapeutic potential of the alcoholic extract of Ulmus pumila L. leaves and the isolated compounds in ameliorating Alzheimer's Disease
The results of the spectrophotometric estimation of total phenolic and flavonoid contents showed that Ulmus pumila L. extract possessed remarkably high amounts of phenols (175.9 Æ 5.2mg) gallic acid equivalent/gram extract and total flavonoid content of 68.7 Æ 1.2 mg rutin equivalent/g extract
Summary
Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders (Calsolaro et al, 2019). Drugs affecting acetylcholine (ACh) levels, basically acetylcholinesterase inhibitors (AChE-Is) were considered for the use as therapeutic agents for AD (Dall'acqua, 2013). From another prospective, the role of neurotrophic factors in regulating neuronal survival and functionality has been recently depicted. Normal neuronal conservation and persistence requires activation of key signaling pathways which are triggered by these factors. It attaches to tropomyosin receptor kinase B (trkB) located on neurons leading to their provision. Transforming growth factor-β1 (TGF-β1) is another neurotrophic factor involved in the signaling pathways that imparts significant protective role in neurons (Wyss-Coray, 2006)
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